Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

In the paper

“Proteostasis failure occurs in C. elegans in response to spaceflight, although it was not clear if this response was due only to muscle wasting (Honda et al., 2012).”

What the sources say

• Disputed

  The Results (page not provided) report that space-flown C. elegans had fewer Q35 protein aggregates than ground controls—the opposite of the claimed proteostasis failure. The Discussion suggests that altered neuronal signaling may affect protein stability in muscle; it does not conclude that spaceflight caused proteostasis failure or attribute such a failure to muscle wasting. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  cites Honda et al., 2012 sourceExperimental — accuracy not yet measured

In the paper

“Astronauts had a decrease in 1,25 vitamin D levels (the active form of vitamin D) (Fig. 5B) consistent with other studies (Smith et al., 2005)”

What the sources say

• Disputed

  The Bone markers section says that 1,25-dihydroxycholecalciferol, the active form of vitamin D, was not different after landing. It was 25-hydroxycholecalciferol—a different measure—that decreased; the paper describes similar findings in earlier studies for that measure. (LLM, conf=0.93)

  Checked by a reasoning model — may be wrong.

  cites Smith et al., 2005 sourceExperimental — accuracy not yet measured

In the paper

“Exposure to space radiation and microgravity are primary hazards to astronauts’ health in long-duration space missions (Garrett-Bakelman et al., 2019).”

What the sources say

• Supported

  The introductory passage indexed under Abstract > Conclusion identifies weightlessness and radiation exposure as spaceflight factors with physiological consequences, and names both among concerns for prolonged missions. The Future missions and conclusions section further discusses health risks from radiation exposure on exploration missions. The paper does not rank hazards explicitly, but it supports the claim’s broad characterization. (LLM, conf=0.85)

  cites Garrett-Bakelman et al., 2019 sourceExperimental — accuracy not yet measured

In the paper

“astronauts that returned from missions on the International Space Station (ISS) presented with health issues similar to geriatric stress, including bone and muscle mass loss, central nervous system issues, immune dysfunction, and cardiovascular health risks (Strollo et al., 2018).”

What the sources say

• Partly supported

  The Introduction (page unavailable) says astronauts returning from long-term space missions have health problems resembling those of older people, particularly involving the immune system, bones, muscles, and cardiovascular system. The CNS Changes section also describes brain changes after long-term spaceflight. The paper does not establish that this full set of problems was observed specifically in astronauts returning from ISS missions; its statement is about long-term space missions generally. (LLM, conf=0.87)

  cites Strollo et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“Phosphorylation of eIF2α reduces the cytosolic initiation complex (eIF2-GTP-Met-initiation tRNA), resulting in the preferential translation of mRNAs with an upstream ORF (uORF1) and activates the ISR (Balsa et al., 2019b; Quiros et al., 2017; Wong et al., 2019).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Balsa et al., 2019b
• Partly supported

  The Results section, “ATF4 is activated through the ISR” (page unavailable), says that eIF2α phosphorylation reduces total protein synthesis while allowing preferential translation of some transcripts with upstream ORFs, such as ATF4 and ATF5. It does not specify a reduction in the eIF2-GTP-Met-initiation-tRNA complex or identify uORF1, so those mechanistic details are not supported by our copy. (LLM, conf=0.84)

  cites Quiros et al., 2017 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page not provided) says eIF2α phosphorylation inhibits eIF2B, triggers the ISR, reduces translation initiation, and increases translation of certain mRNAs with special 5′-UTR sequences. It identifies the eIF2-GTP-Met-tRNAi complex but does not explicitly say its cytosolic abundance falls or specify an upstream ORF called uORF1. (LLM, conf=0.83)

  cites Wong et al., 2019 sourceExperimental — accuracy not yet measured

In the paper

“We focused on the liver since we previously demonstrated that the liver regulates immune activity and lipid dysregulation during spaceflight (Beheshti et al., 2019).”

What the sources say

• Partly supported

  The Results ("Duration changes in livers from mice flown in space"; page unavailable) report increased adaptive-immune and fatty-acid pathways in mouse liver with longer spaceflight, alongside liver lipid accumulation. The paper does not demonstrate that the liver itself regulates immune activity or causes lipid dysregulation during spaceflight; it documents changes in liver tissue. (LLM, conf=0.84)

  cites Beheshti et al., 2019 sourceExperimental — accuracy not yet measured

In the paper

“For example, oxidative stress activates four kinases (GCN2, PKR, HRI, PERK) that initiate the ISR by regulating the phosphorylation of the cytosolic translation elongation factor 2 alpha (eIF2α) (Pakos-Zebrucka et al., 2016).”

What the sources say

• Partly supported

  The Activation section says all four eIF2α kinases become activated in response to oxidative stress, and the figure description says they converge on eIF2α phosphorylation at the core of the ISR. However, the citing sentence calls eIF2α a translation *elongation* factor; the Introduction identifies it as a translation *initiation* factor. (LLM, conf=0.90)

  cites Pakos-Zebrucka et al., 2016 sourceExperimental — accuracy not yet measured

In the paper

“The astronaut in the Twin Study passed only 2% of his lifespan in space (Garrett-Bakelman et al., 2019), whereas the mice from the RR1 and RR3 missions passed approximated 25% of their lifespan at the ISS.”

What the sources say

• Supported

  The Results report that the flight subject was 50 years old at study initiation and spent 340 days aboard the ISS during the Twins Study mission. That mission was approximately 1.9% of his lifespan to that point, consistent with the cited 2% figure. The citation is attached to the astronaut comparison, not the statement about mice. (LLM, conf=0.90)

  cites Garrett-Bakelman et al., 2019 source

In the paper

“pathways linked to inflammation-induced muscle wasting (Londhe and Guttridge, 2015).”

What the sources say

• Partly supported

  The sections on IFN-γ and TNF-α link those cytokines to impaired muscle differentiation, damage, or loss of muscle mass. The IL-10 and IL-17 sections mention IL-1 as a pro-inflammatory cytokine, but do not link an IL-1 pathway specifically to muscle wasting. No page numbers were available in our copy. (LLM, conf=0.88)

  cites Londhe and Guttridge, 2015 sourceExperimental — accuracy not yet measured

In the paper

“linking oxidative stress and mitochondrial dysfunction (Massudi et al., 2012).”

What the sources say

• Partly supported

  The “NAD+ in energy metabolism” section describes NAD+/NADH roles in mitochondrial respiration, and “Oxidative damage targets and types” connects NAD+ concentrations with redox potential. The paper does not establish that NAD metabolism is upregulated in the liver or that such upregulation links oxidative stress to mitochondrial dysfunction; its liver discussion concerns the size of the mitochondrial NAD+ pool. (LLM, conf=0.84)

  cites Massudi et al., 2012 sourceExperimental — accuracy not yet measured

In the paper

“Increased prostaglandin F2 alpha levels in urine are associated with oxidative stress and cyclooxygenase independent synthesis (Yin et al., 2007).”

What the sources say

• Supported

  The paper states that urinary PGF2α reflects oxidative stress and reports elevated levels in conditions associated with oxidant stress. Its Discussion says the majority of PGF2α in human urine comes from the isoprostane pathway rather than cyclooxygenase, supporting the claim in the verbatim citing sentence. (LLM, conf=0.91)

  cites Yin et al., 2007 source

In the paper

“A recent comprehensive meta-analysis across similar studies found increased risks of NAFLD and liver fibrosis in subjects with sarcopenia (Cai et al., 2020).”

What the sources say

• Supported

  The Results sections report higher pooled odds of NAFLD in subjects with sarcopenia (OR 1.33) and of NAFLD-related significant fibrosis among NAFLD patients with sarcopenia (OR 1.56), compared with their respective controls. This supports the citing sentence’s summary; the fibrosis finding is specifically about NAFLD-related significant fibrosis. (LLM, conf=0.94)

  cites Cai et al., 2020 source

In the paper

“An increase in ROS, as encountered in spaceflight, triggers adult stem cells differentiation, and rapidly switches to mitochondrial OXPHOS (Hamanaka et al., 2013; Ito and Suda, 2014).”

What the sources say

• Partly supported

  The Introduction reports that mitochondrial ROS are required for differentiation of human bone marrow–derived mesenchymal stem cells into adipocytes, and the Results show that ROS support keratinocyte differentiation. The paper does not establish that spaceflight-associated ROS trigger adult stem-cell differentiation or cause a rapid switch to mitochondrial OXPHOS. The indexed passages provide section labels but no page numbers. (LLM, conf=0.88)

  cites Hamanaka et al., 2013 sourceExperimental — accuracy not yet measured
• Partly supported

  The sections “Glycolysis and HIF in other adult stem cells” and “Switch to oxidative metabolism” say that ROS induced under normoxia can move adult stem cells out of quiescence and may prime differentiation, while differentiating HSCs need a rapid switch to mitochondrial OXPHOS. They do not establish that increased ROS directly triggers that switch or differentiation, and they do not address spaceflight. The copy provides section labels but no page numbers. (LLM, conf=0.87)

  cites Ito and Suda, 2014 sourceExperimental — accuracy not yet measured

In the paper

“The existence of spaceflight-induced mitochondrial stress is further supported by metabolite studies reporting increased urinary 8-OHdG and prostaglandin F2 alpha.”

• Also stated in: § Discussion · hedged

  “These markers are consistent with our analysis suggesting mitochondrial stress and dysfunction due to oxidative stress during spaceflight (Figs. 3B, 3F, and 3G).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wu et al., 2004
• Partly supported

  The Results section reports elevated urinary PGF2α in smokers and people with hypercholesterolemia and describes it as a potential marker of oxidative stress. The paper does not report spaceflight exposure, mitochondrial stress, or urinary 8-OHdG, so it cannot substantiate the sentence’s spaceflight-specific conclusion. (LLM, conf=0.87)

  cites Yin et al., 2007 sourceExperimental — accuracy not yet measured

In the paper

“and the results from our analyses are consistent with those from previous studies (Beheshti et al., 2019; Suomalainen and Battersby, 2018) and are supported by multiple other omics studies (Bezdan et al., 2020; Gertz et al., 2020).”

What the sources say

• Supported

  Beheshti et al. is cited for consistency with previous studies, not for the separate claim about other omics studies. In the Results section, the paper compares its mouse-liver findings with Jonscher et al.’s earlier findings on spaceflight-related lipid accumulation and PPARα signaling. No page number is available in our copy. (LLM, conf=0.86)

  cites Beheshti et al., 2019 source
• ?Not checked — no full text of the sourcecites Suomalainen and Battersby, 2018 source
• Supported

  The citation to Bezdan et al. is attached to the reference to other omics studies, not to the preceding claim about consistency with previous studies. The Discussion (page unavailable) identifies this work as part of a longitudinal, multi-omic spaceflight study and reports cfDNA and exosome findings, so it supports its use as an example of such a study. (LLM, conf=0.87)

  cites Bezdan et al., 2020 source

In the paper

“Increased oxidative stress and mitochondrial stress were implicated in causing androgenetic alopecia (permanent hair loss) (Ho et al., 2019; Upton et al., 2015).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ho et al., 2019
• Partly supported

  The Abstract (page unavailable) says the in vitro findings suggest a role for oxidative stress in the pathogenesis of androgenetic alopecia. The paper does not identify mitochondrial stress as a contributor, and its evidence suggests a possible role rather than establishing that oxidative stress causes the condition. (LLM, conf=0.87)

  cites Upton et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Microgravity-induced muscle degeneration is well reported (Demontis et al., 2017; Nikawa et al., 2004).”

What the sources say

• Supported

  The “Effects on the musculoskeletal system” section (page not provided) states that prolonged microgravity exposure causes muscle-mass loss and that the degree of loss varies with exposure duration. This supports the citing sentence’s broad description of microgravity-induced muscle degeneration. (LLM, conf=0.94)

  cites Demontis et al., 2017 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Nikawa et al., 2004 source

In the paper

“Skeletal muscle also depends on OXPHOS for energy production (Kelley et al., 2002) reported to play a role in regulating metabolism (Argiles et al., 2016; Pratesi et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Kelley et al., 2002 source
• Partly supported

  The Summary and Conclusions (page unavailable) identify skeletal muscle as a regulator of energy and protein metabolism. The Muscle Metabolism and Interorgan Crosstalk section describes aerobic metabolism in slow muscle fibers, but does not say that OXPHOS itself regulates metabolism. The claim that muscle depends on OXPHOS for energy production is attached to Kelley et al., not this source. (LLM, conf=0.82)

  cites Argiles et al., 2016 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Pratesi et al., 2013

In the paper

“Several conditions that lead to liver fibrosis are known to be marked by specifically dysregulated metabolic pathways, including significant increases in metabolites involved in glycolysis/gluconeogenesis, fructose and mannose metabolism, tryptophan metabolism, valine, leucine, isoleucine metabolism, glycine, serine, and threonine metabolism, glutathione metabolism, glycerophospholipid metabolism,”

What the sources say

• Partly supported

  Section 4.2 (Animal Studies; page unavailable) reports alterations across the listed pathways in rat models of hepatic fibrosis, including CCl4-treated rats, but generally describes the metabolites as altered or perturbed, not significantly increased. Section 3.2 reports decreased branched-chain amino acids, including valine, leucine, and isoleucine, in some models, so the claim’s blanket assertion of increases is not supported. (LLM, conf=0.89)

  cites Chang and Yang, 2019 sourceExperimental — accuracy not yet measured

In the paper

“PGC1α also interacts with PPARγ, and dysregulation of PPARγ has been shown in hair follicle stem cells (HFSCs) to produce similar results to scarring alopecia (i.e., hair loss disorder) (Karnik et al., 2009).”

What the sources say

• Partly supported

  The Introduction and Discussion (page numbers unavailable) report that deleting PPARγ in mouse hair follicle stem cells causes scarring alopecia resembling human disease. The cited paper’s passages do not establish the separate claim that PGC1α interacts with PPARγ. (LLM, conf=0.88)

  cites Karnik et al., 2009 sourceExperimental — accuracy not yet measured

In the paper

“mitochondrial dysfunction attenuates platelet survival and increased risk for thrombovascular events (Kunz et al., 2017; Melchinger et al., 2019), increasing stroke risk (Behrouzi and Punter, 2018).”

What the sources say

• ?Could not verify

  The Results report platelet concentrations during spaceflight, and the Discussion considers plasma-volume changes as a possible explanation. Neither passage addresses mitochondrial dysfunction, platelet survival, or thrombovascular events; searches for those terms found no supporting passage. The stroke-risk clause is separately cited to another source. (LLM, conf=0.76)

  cites Kunz et al., 2017 sourceExperimental — accuracy not yet measured
• Partly supported

  The sections on platelet survival and disease link mitochondrial damage to premature platelet death and apoptotic platelets to faster clotting. The paper says preserving mitochondrial function may reduce thrombotic-event risk in diabetic patients, but does not establish the claim’s broader, unqualified increase in thrombovascular risk. The stroke-risk clause is cited to Behrouzi and Punter, not to this paper. (LLM, conf=0.83)

  cites Melchinger et al., 2019 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction identifies cerebral venous thrombosis (CVT) as a cause of stroke and says a cerebral venous thrombus can lead to infarction. That supports a link between CVT and stroke, but the paper does not establish that thrombovascular events generally increase stroke risk. The platelet-survival and mitochondrial-dysfunction claims are attributed to other citations, not this one. (LLM, conf=0.82)

  cites Behrouzi and Punter, 2018 sourceExperimental — accuracy not yet measured

In the paper

“IFN-γ can induce a switch to aerobic glycolysis and has a significant role in proteasome regulation (Wang et al., 2018; Yang et al., 1992), linking mitochondrial dysfunction, innate immunity, and alterations in proteostasis.”

What the sources say

• Partly supported

  The Introduction and Results report that IFN-γ increases aerobic glycolysis in macrophages, followed by reduced oxidative phosphorylation, and link that shift to mitochondrial ROS and inflammatory signaling (page numbers not supplied). The cited paper does not establish a role for IFN-γ in proteasome regulation or connect its findings to alterations in proteostasis. (LLM, conf=0.87)

  cites Wang et al., 2018 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Yang et al., 1992 source

In the paper

“Increased tryptophan, valine, leucine, isoleucine, TCA cycle, sphingolipid, and glycerophospholipid metabolites are reported in the development and onset of fibrosis, with valine and bile acid synthesis related to more advanced stages (Chang and Yang, 2019; Musso et al., 2018).”

What the sources say

• Partly supported

  Section 4.2 (Animal Studies) reports perturbations in the listed metabolites from the onset of hepatic fibrosis and dysregulation of valine and bile acid biosynthesis metabolites at intermediate and advanced stages. It does not say those metabolites increased; Section 3.2 reports decreased valine, leucine, and isoleucine in some fibrotic rat models. The claim also omits that the stage-specific finding came from CCl4-treated rats. (LLM, conf=0.89)

  cites Chang and Yang, 2019 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Musso et al., 2018 source

In the paper

“Vitamin D can modulate the innate and adaptive immune responses as the vitamin D receptor is expressed on B cells, T cells, antigen-presenting cells, and dendritic cells (Aranow, 2011).”

What the sources say

• Supported

  The Abstract states that vitamin D can modulate innate and adaptive immune responses and that its receptor is expressed on B cells, T cells, and antigen-presenting cells. It also identifies dendritic cells as antigen-presenting cells with the machinery to respond to vitamin D. (LLM, conf=0.94)

  cites Aranow, 2011 source

In the paper

“Two mouse strains were previously found to have accumulated lipids in the liver due to spaceflight exposure (Beheshti et al., 2019).”

What the sources say

• Supported

  The Discussion states that lipid uptake in the liver occurred in both mouse strains, with a stronger response in C57BL/6J. The Results identify the comparison as space-flown mice versus ground controls, supporting the attribution to spaceflight exposure. (LLM, conf=0.91)

  cites Beheshti et al., 2019 source

In the paper

“Cardiovascular disease is also linked to mitochondrial dysfunction through proteostasis failure related to lipid accumulation and ROS activity (Alam et al., 2020; Arrieta et al., 2020).”

What the sources say

• Partly supported

  The Introduction links impaired protein quality control and mitochondrial dysfunction to cardiac disease. The section “Electron Transport Chain and Oxidative Stress in Cardiac Proteostasis” links mitochondrial ROS, proteasome inhibition, and aggregate accumulation to cardiac proteotoxicity. It discusses accumulation of lipofuscin, not lipid accumulation generally, so that part of the claim is not supported. (LLM, conf=0.86)

  cites Alam et al., 2020 sourceExperimental — accuracy not yet measured
• Partly supported

  The 'Mitochondrial Proteostasis' section links disrupted mitochondrial protein quality control to impaired ATP production and cardiac function. 'Mitochondrial Proteostasis in Cardiac Pathology' reports increased reactive oxygen species after protease knockdown, but that finding was in myoblasts, not the heart. The passages do not link lipid accumulation to this proposed cardiovascular-disease pathway (page numbers unavailable). (LLM, conf=0.85)

  cites Arrieta et al., 2020 sourceExperimental — accuracy not yet measured

In the paper

“dysregulation of adaptive immunity occurring during spaceflight, consistent with an increased innate immunity profile on spaceflight (Crucian et al., 2018).”

What the sources say

• Supported

  The Discussion (page not available in our copy) describes diminished T/NK-cell function alongside increased inflammatory plasma cytokine levels during six-month orbital flight. This supports the cited sentence’s characterization of dysregulated adaptive immunity and a heightened innate-inflammatory profile. (LLM, conf=0.86)

  cites Crucian et al., 2018 source

In the paper

“IFN-γ, IL-1, and TNF-α are known to be drivers of muscle wasting in chronic inflammatory diseases (Londhe and Guttridge, 2015).”

What the sources say

• Supported

  The section on polymyositis and inclusion body myositis names TNF-α, IFN-γ, and IL-1 as cytokines thought to have toxic effects on skeletal muscle. The review’s summary says pro-inflammatory cytokines are major contributors to muscle loss in chronic inflammatory diseases; its rheumatoid arthritis section also identifies TNF-α and IL-1 as likely mediators of muscle wasting. Our copy provides section labels but no page numbers. (LLM, conf=0.87)

  cites Londhe and Guttridge, 2015 source

In the paper

“proteostasis loss is a hallmark of aged muscles (Fernando et al., 2019).”

What the sources say

• Supported

  Section 2 calls loss of proteostasis an important and consistent feature of muscle aging and says it has been proposed as a major hallmark of aging. Section 3 is titled “Proteostasis loss as a hallmark of aged muscle.” (LLM, conf=0.95)

  cites Fernando et al., 2019 source

In the paper

“Mitochondrial dysfunction inhibits cytosolic protein synthesis and defective protein quality control (Lu and Guo, 2020; Topf et al., 2019).”

What the sources say

• Partly supported

  The section “Mitochondrial Outer Membrane-Associated Translation is Stalled by Mitochondrial Stress” (page unavailable) reports that persistent mitochondrial damage stalls translation of a specific mRNA at the mitochondrial outer membrane. The paper also links mitochondrial stress to altered protein quality control, but it does not establish that mitochondrial dysfunction broadly inhibits cytosolic protein synthesis or necessarily makes protein quality control defective. (LLM, conf=0.84)

  cites Lu and Guo, 2020 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Topf et al., 2019 source

In the paper

“mitochondrial dysfunction is both a cause and a consequence of metabolic disorders (Bhatti et al., 2017).”

What the sources say

• Supported

  Section 8 describes mitochondrial dysfunction as contributing to components of metabolic syndrome and also describes obesity as contributing to mitochondrial dysfunction. Section 5 likewise reports that elevated glucose can produce ROS that changes mitochondrial structure. Together, these passages support the bidirectional claim. (LLM, conf=0.90)

  cites Bhatti et al., 2017 source

In the paper

“Vitamin D3 is modified through the mitochondria in the liver and kidney to assume its active form, 1,25 vitamin D (Bikle, 2014).”

What the sources say

• Partly supported

  The Summary and Conclusions and the 1α-hydroxylase section describe conversion of vitamin D to active 1,25(OH)2D, with the kidney the main source of its circulating form. The 25-hydroxylase section reports mitochondrial activity in the liver, but identifies the most important hepatic enzyme, CYP2R1, in the microsomal fraction. Thus the claim overstates that conversion proceeds through mitochondria in both organs. Page numbers were not supplied. (LLM, conf=0.87)

  cites Bikle, 2014 sourceExperimental — accuracy not yet measured

In the paper

“opposite trends in mitochondrial activity in liver and muscle are common in subjects with prediabetes or diabetes type 2 (Bhansali et al., 2017; Pottecher et al., 2018).”

What the sources say

• ?Could not verify

  The Materials and Methods (PBMCs Isolation; no page available) show that mitochondrial measures came from peripheral blood mononuclear cells, not liver and muscle. The Discussion describes differences between prediabetes and type 2 diabetes, but no passage establishes opposite trends in mitochondrial activity between liver and muscle in either group. (LLM, conf=0.75)

  cites Bhansali et al., 2017 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and Discussion describe impaired skeletal-muscle mitochondrial function in diabetes, including type 2 diabetes. The paper does not report liver mitochondrial activity or establish that opposite liver–muscle trends are common in people with prediabetes or type 2 diabetes. Its own experiments concern skeletal muscle in rats with a type 1 diabetes phenotype. (LLM, conf=0.86)

  cites Pottecher et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“Mitochondrial debris were observed in blood in the Twin Study (Garrett-Bakelman et al., 2019) and mitochondrial damage-associated molecular patterns (DAMPs) activate innate immune pathways (Banoth and Cassel, 2018; Zhang et al., 2010).”

What the sources say

• Partly supported

  In Results, “Mitochondria-related adaptations during spaceflight” (page unavailable), the study reports mitochondrial DNA measured in blood plasma and increased mitochondrial RNA during flight. It does not identify the material in blood as mitochondrial debris. The DAMPs clause is attributed to other citations, not this paper. (LLM, conf=0.82)

  cites Garrett-Bakelman et al., 2019 sourceExperimental — accuracy not yet measured
• Supported

  The 'Mitochondria and innate immune responses' section (page not provided) says mitochondrial DAMPs are sensed by receptors that trigger the innate immune response. The Twin Study observation is attributed to Garrett-Bakelman et al., not to Banoth and Cassel. (LLM, conf=0.94)

  cites Banoth and Cassel, 2018 source
• Supported

  The Zhang et al. citation is attached to the claim that mitochondrial DAMPs activate innate immune pathways, not to the Twin Study observation. The Abstract states that mitochondrial DAMPs activate human neutrophils through formyl peptide receptor-1 and TLR9 and signal through innate immune pathways. (LLM, conf=0.94)

  cites Zhang et al., 2010 source

In the paper

“Early in 2020, the first occurrence of venous thrombosis was reported during spaceflight (Aunon-Chancellor et al., 2020).”

What the sources say

• Partly supported

  The Abstract reports a confirmed venous thrombosis in an astronaut during an International Space Station mission, and the copy carries a 2020 copyright notice. It does not say this was the first occurrence during spaceflight or establish that it was reported early in 2020. (LLM, conf=0.84)

  cites Aunon-Chancellor et al., 2020 sourceExperimental — accuracy not yet measured

In the paper

“Cell cycle and mitochondrial activity directly control circadian rhythm in cells and organisms (Sardon Puig et al., 2018).”

What the sources say

• Partly supported

  The Mitochondrial Dynamics section (page unavailable) reports that disrupting a mitochondrial-dynamics protein alters clock-gene oscillations in mouse cells, supporting a link between mitochondrial activity and circadian rhythms. The Conclusion (page unavailable) describes mitochondrial effects on the clock as possible mechanisms, not established direct control across cells and organisms. The cited passages do not support the separate claim about the cell cycle. (LLM, conf=0.88)

  cites Sardon Puig et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“The combination of replicating mtDNA and ROS would oxidize the mtDNA, which would be released to activate the innate immune system inflammasome and the Type I interferon pathway (West and Shadel, 2017; Zhong et al., 2018).”

What the sources say

• ?Not checked — no full text of the sourcecites West and Shadel, 2017 source
• Partly supported

  The Discussion (page unavailable) links newly synthesized mtDNA, oxidation, release of ox-mtDNA fragments, and NLRP3 inflammasome activation. The paper does not show that released ox-mtDNA activates the type I interferon pathway; its discussion of IRF1 concerns an upstream regulator of mtDNA synthesis and NLRP3 activation. (LLM, conf=0.88)

  cites Zhong et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“They also regulate a wide range of cellular processes, including a significant role in synapse formation and elimination, affecting memory formation (Leung and Wong, 2017; Ye and Carew, 2010).”

What the sources say

• Supported

  The Introduction (page unavailable) links synapse formation and structural plasticity to learning and memory. Sections 2.1 and 2.3 (pages unavailable) describe G-protein signalling pathways that affect spine morphology and memory processes. The review therefore supports the claim as a broad paraphrase, rather than as evidence that every G protein directly controls synapse formation and elimination. (LLM, conf=0.86)

  cites Leung and Wong, 2017 source
• Partly supported

  The Abstract says small G-proteins regulate a wide range of cellular processes, and the Regulation of Structural Plasticity section says Ras family proteins can regulate synapse structure, including processes involved in new synapse growth. That section mentions synapse elimination in connection with mental retardation, but does not establish that these proteins regulate elimination; it also describes the link between structural changes and memory storage as proposed. (LLM, conf=0.84)

  cites Ye and Carew, 2010 sourceExperimental — accuracy not yet measured

In the paper

“Immune dysregulation is known to be strongly influenced by the cell cycle (Laphanuwat and Jirawatnotai, 2019).”

What the sources say

• Supported

  The Summary and Outlook states that cell cycle regulators help orchestrate immune functioning and that interfering with CDK activity can lead to weakened immunity, autoimmunity, or immunotolerance. This supports the broad claim that the cell cycle strongly influences immune dysregulation. (LLM, conf=0.90)

  cites Laphanuwat and Jirawatnotai, 2019 source

In the paper

“The reduced NADH and radiation-induced DNA damage would reduce NAD+ levels (Fig. 3G), which would impair the circadian rhythm system through perturbed Sirt1 regulation of BMAL acetylation (Nakahata et al., 2008).”

What the sources say

• Supported

  The Results section reports that SIRT1 deacetylates BMAL1 in an NAD+-responsive manner (BMAL1 Acetylation at Lys537 Is Regulated by SIRT1) and that loss of SIRT1 disrupts rhythmic BMAL1 acetylation and circadian gene expression (SIRT1 Contributes to Circadian Control In Vivo). Those findings support the cited mechanism. The preceding claim about reduced NAD+ is linked to the citing document’s own Fig. 3G, not established by this citation. (LLM, conf=0.89)

  cites Nakahata et al., 2008 source

In the paper

“G protein-coupled receptor kinase 2 (GRK2) was reported to act as a gatekeeper of mitochondrial function in the heart, and the inhibition of G protein-coupled receptor 35 (GPR35) preserved mitochondrial function after myocardial infarction (Chen et al., 2020; Sorriento et al., 2019).”

What the sources say

• Supported

  Chen et al. supports the GPR35 portion of the sentence; the GRK2 statement appears to be associated with the other citation. The Discussion states that inhibiting GPR35 alleviates myocardial-infarction injury by preserving mitochondrial function. (LLM, conf=0.93)

  cites Chen et al., 2020 source
• Supported

  Sorriento et al. (2019) supports the GRK2 portion of the sentence: its section ‘GRK2 in Mitochondria: Detrimental or Cardioprotective?’ describes GRK2’s role in protecting mitochondrial function in damaged cardiac cells. The sentence also cites Chen et al. (2020); the GPR35 finding is not the part attributable to this GRK2-focused review. Our copy provides section labels but no page numbers. (LLM, conf=0.90)

  cites Sorriento et al., 2019 source

In the paper

“CoQ10 is an abundant lipid-soluble nutrient scavenging free radical and protecting cells against oxidative damage (Zhang et al., 2018).”

What the sources say

• Supported

  The Introduction states that CoQ10 is a lipid-soluble nutrient widely present in living cells and that, as an antioxidant, it scavenges free radicals and protects cells from oxidation. This supports the citing sentence’s paraphrase. (LLM, conf=0.94)

  cites Zhang et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“the increases of acute inflammatory markers seen during exercise (e.g., IL-6, TNF-a, IL1-RA, and IGF-1) could be problematic to an already increased inflammatory pattern we measured in astronauts (Fig. 5B), even though these markers are reduced by regular exercise in low-grade systemic inflammation patients (Contrepois et al., 2020; Khazaei, 2012).”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites Contrepois et al., 2020 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Khazaei, 2012

In the paper

“Olfactory signaling has even been directly linked to mitochondrial structure and glucose activity (Kovach et al., 2016), indicating we have uncovered a systemic impact on the body driven by the mitochondria.”

What the sources say

• Supported

  The Introduction reports glucose signaling in olfactory-bulb mitral cells, and the Abstract reports that the study examined mitochondrial ultrastructure in those cells. Together, these support the cited link between olfactory signaling, mitochondrial structure, and glucose activity. The sentence’s claim of a systemic impact is framed as the citing authors’ own inference, not a finding attributed to Kovach et al. (LLM, conf=0.88)

  cites Kovach et al., 2016 source

In the paper

“Sleep disorders are common in astronauts (Wu et al., 2018) and patients with primary mitochondrial diseases (Ramezani and Stacpoole, 2014).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wu et al., 2018
• Partly supported

  The Results report subjective sleep dysfunction in 15 of 20 patients evaluated at one neuromuscular center. But the Discussion says the prevalence of sleep pathology across patients with primary mitochondrial diseases is unknown and requires population-based studies, so the unqualified claim that it is common is not established. The astronaut clause is attributed to a different citation and is not assessed here. (LLM, conf=0.84)

  cites Ramezani and Stacpoole, 2014 sourceExperimental — accuracy not yet measured

In the paper

“G proteins are ubiquitous inside cells and play an essential role in circadian regulation (Doi et al., 2011).”

What the sources say

• Partly supported

  The Discussion (page not provided) says that regulated intracellular G-protein signalling in the suprachiasmatic nucleus helps coordinate its neurons and contributes to the period of daily behavioural rhythms. This supports a role in circadian regulation, but the paper does not establish that G proteins are ubiquitous inside cells or that this role applies generally across cells. (LLM, conf=0.86)

  cites Doi et al., 2011 sourceExperimental — accuracy not yet measured

In the paper

“mitochondrial Ca(2+) is a critical element in olfactory signaling (Fluegge et al., 2012) and in astronauts, smelling behavior changes occur potentially due to microgravity causing an upward shift of body fluid (Mukhopadhyay et al., 2016).”

What the sources say

• ?Not checked — no full text of the sourcecites Fluegge et al., 2012 source
• Supported

  The Mukhopadhyay et al. citation is attached to the claim about astronauts’ changed smelling behavior and a possible fluid-shift explanation, not the preceding mitochondrial Ca(2+) claim. The Discussion reports that the behavior change was documented and that a microgravity-induced upward shift of body fluid was postulated as a plausible reason. (LLM, conf=0.93)

  cites Mukhopadhyay et al., 2016 source

In the paper

“ROS causes T cell cycle arrest (Belikov et al., 2015; Yan and Banerjee, 2010) and T cell activation/proliferation requires a reducing extracellular microenvironment (Yan and Banerjee, 2010).”

What the sources say

• Partly supported

  The Review section “T cells and oxidative stress” (page unavailable) reports that neutrophil-derived ROS inhibit DNA synthesis in human T cells and negatively affect their proliferation. It does not establish cell-cycle arrest specifically, and its finding concerns excessive, phagocyte-derived ROS rather than ROS in general. The reducing-extracellular-microenvironment clause is cited only to Yan and Banerjee, so it is not assessed against Belikov et al. (LLM, conf=0.84)

  cites Belikov et al., 2015 sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract and Concluding Remarks state that T-cell activation and proliferation require a reducing extracellular microenvironment. The “Redox Signaling During T cell Activation” section says sustained pro-oxidant conditions inhibit proliferation, but does not establish that ROS causes T-cell cycle arrest; it also says low levels of ROS can promote activation. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  cites Yan and Banerjee, 2010 sourceExperimental — accuracy not yet measured

In the paper

“The strongest candidate is the coenzyme Q10 (CoQ10) that should be administered to the majority of primary mitochondrial diseases (PMD), independent of CoQ10 deficiency (Camp et al., 2016).”

What the sources say

• Supported

  Section 4.3 recommends CoQ10 for most patients diagnosed with mitochondrial disease, not only those with primary CoQ10 deficiency. Its broader recommendation than those for other supplements supports the characterization of CoQ10 as the strongest candidate; the section does not establish that it is the most effective treatment. (LLM, conf=0.88)

  cites Camp et al., 2016 source

In the paper

“The field of nutritional mitochondrial therapeutics is still evolving, with some evidence pointing to effective treatments (Camp et al., 2016; Rinninella et al., 2018).”

What the sources say

• Supported

  Section 2.3 describes mitochondrial medicine as a young specialty with a limited evidence base. Section 4.2 reports a small controlled trial in which a nutritional supplement combination produced statistically significant improvements in several measures, supporting the claim’s cautious wording that some evidence points to effective treatments. The paper also emphasizes that efficacy remains insufficiently established for many interventions. (LLM, conf=0.88)

  cites Camp et al., 2016 source
• ?Not checked — no full text of the sourcecites Rinninella et al., 2018 source

In the paper

“A study on acute exercise in individuals with a spectrum of insulin resistance showed that acute physical activity triggers molecular responses on the metabolic and energy-producing pathways, increasing glycolysis, TCA cycle, and fatty acid oxidation (Contrepois et al., 2020).”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Contrepois et al., 2020 source

In the paper

“Cell cycle pathways were upregulated in all cell and tissue models except in human T cells, where these same terms were downregulated (Fig. 7A and 7B).”

In the paper

“reduced antioxidant defenses and increased urinary markers of oxidative stress (Fig. 3F)”

In the paper

“Overall pathway analyses on the multi-omic datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions.”

In the paper

“Observed changes include altered mitochondria-associated metabolites and modified nDNA and mtDNA OXPHOS gene expression (Fig. 3B), reduced antioxidant defenses and increased urinary markers of oxidative stress (Fig. 3F), and altered integrated stress response (ISR) gene expression (Fig. 3C).”

In the paper

“Liver contained the most mitochondrial activity across all organs, while the soleus and EDL had the most mitochondrial activity amongst the muscles (Fig. 2E).”

In the paper

“Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.”

In the paper

“Finally, we observed the downregulation of the stress response genes Fgf21 or Gdf15 in liver or soleus muscle, respectively.”

In the paper

“In the RR3 mission, Gadd34 was down-regulated in the oxidative soleus muscle and upregulated in the glycolytic anterior tibialis muscle, while the stress gene Atf5 was upregulated in both the anterior tibialis and in the EDL muscle, which is also a predominantly glycolytic muscle.”

In the paper

“Immune response through interferon-gamma (IFN-γ) and interferon-alpha (IFN-α) gene sets were down-regulated in the kidney and liver (Fig. 4B), with the epigenetic analysis showing differential methylation of these same gene sets (Fig. 5A).”

In the paper

“While we observed an increase in mtDNA gene expression in the Twin Study, spaceflight reduced astronauts’ antioxidant capacity (Fig. 3F), coupled with an increase in urinary markers of oxidative stress including 8OHdG and Prostaglandin F2 alpha (PDGF2-alpha) (Table S4 and Fig. 3F).”

In the paper

“From our analysis of tissue pathways, lipid metabolism gene sets were upregulated in the liver and kidneys and downregulated in the eyes and adrenal gland (Fig. 6A).”

In the paper

“In contrast, there were no robust changes in any of the genes from matched samples for the twin on Earth or in GAPDH, a key cytosolic enzyme in the glycolytic pathway.”

In the paper

“In the EDL, a highly glycolytic tissue, we observed higher levels of mtDNA OXPHOS genes (mt-Co1, mt-Co3, mt-Nd4, mt-Nd4l, mt-Nd5, mt-Atp6), although nDNA-coded mitochondrial genes were not decreased (Fig. 3B).”

In the paper

“Modeled flux through the citric acid cycle (CAC) gatekeeping enzyme Citrate Synthase (CSm, Fig. 6C–6D) in FLT vs GC significantly decreased in muscle but was up in liver.”

In the paper

“At the epigenetic level, only EDL and GST muscles showed altered methylation, with EDL showing alteration in the IFN-α (Fig. 5A).”

In the paper

“The CAC malate dehydrogenase (MDHm) flux that converts malate to oxaloacetate is significantly reduced in FLT vs GC muscle, as are mitochondrial Carnitine O acetyltransferase (CSNATm), which converts carnitine into acetyl carnitine, and Malonyl-CoA Decarboxylase (MCD), which converts the fatty acid metabolism antagonist malonyl-CoA (Brady et al., 1993) (Fig. 6C–6D).”

What the sources say

• ?Not checked — no full text of the sourcecites Brady et al., 1993 source

In the paper

“We found higher levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, accompanied by decreased levels of high-density lipoprotein (HDL) cholesterol.”

In the paper

“The third major grouping of GSEA pathway hits focused on lipid biology.”

In the paper

“CD19 cells had the greatest increase in mitochondrial activity post-flight for the twin in space, while mitochondrial activity in the CD4 population was significantly reduced in-flight and post-flight (Fig. 3D).”

In the paper

“Our analysis from the cell line data shows hair follicles exhibit increased expression of genes related to mitochondrial activity, while other cells show reduced expression (Fig. 2A).”

In the paper

“ECM related pathways were unaltered in the quadriceps, upregulated in SLS, EDL, GST, and TA muscles, and downregulated in the carotid artery (Fig. 7C).”

In the paper

“The reduction of muscle metabolic flux when comparing between FLT vs GC vs the opposite result in liver (Figs. 3G, 6C, and 6D)”

In the paper

“The complement system and pathways related to IFN-γ and IFN-α change in the internal organs (Fig. 4B).”

In the paper

“Spaceflight caused an increased expression of cell cycle genes in fibroblasts, endothelial cells, and the hair follicles, but these genes were down-regulated in T cells (Fig. 7A).”

In the paper

“In addition to the known increased cancer risk from chronic low doses of radiation exposure (Durante and Cucinotta, 2008), astronauts that returned from missions on the International Space Station (ISS) presented with health issues similar to geriatric stress, including bone and muscle mass loss, central nervous system issues, immune dysfunction, and cardiovascular health risks (Strollo et al., 2”

What the sources say

• ?Not checked — no full text of the sourcecites Durante and Cucinotta, 2008 source

In the paper

“Second, the liver undergoes more differential gene and protein expression changes than other organs, consistent with the role the liver plays as a dynamic and critical hub in sensing changes in blood composition and maintaining homeostasis.”

In the paper

“These and related observations suggest that mitochondrial dysfunction may alter metabolic flux through mitochondrial pathways, perturb mitochondrial gene expression, and activate the ISR.”

In the paper

“These observations support the conclusion that spaceflight suppresses nDNA-coded mitochondrial OXPHOS gene expression predominantly in oxidative tissues, and the induction of the mtDNA genes partially compensates for the diminished mitochondrial oxidative metabolism.”

In the paper

“We did not assess dietary intake before or after spaceflight.”

In the paper

“Urinary 8-OHdG is a biomarker of generalized cellular oxidative stress, a marker of oxidized DNA that signals that DNA repair is occurring, and a risk factor for cancer, atherosclerosis, and diabetes (Wu et al., 2004).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wu et al., 2004

In the paper

“These results indicate that spaceflight impacts lipid metabolism at the hepatic gene expression level, extending to the circulating lipid profile.”

In the paper

“a particularly important consideration given the recent findings that mice and humans have different biochemical reaction speeds that affect development (Matsuda et al., 2020).”

What the sources say

• ?Not checked — no full text of the sourcecites Matsuda et al., 2020 source

In the paper

“From the murine perspective, this was a long-term space mission, a particularly important consideration given the recent findings that mice and humans have different biochemical reaction speeds that affect development (Matsuda et al., 2020).”

In the paper

“Therefore Atf5, Chop, and Gdf15 are downregulated in oxidative muscle during spaceflight, consistent with reduced ISR.”

In the paper

“Nikawa and collaborators proposed a spaceflight-specific, induced mitochondrial activity alteration associated with muscle atrophy in 2004 (Nikawa et al., 2004).”

What the sources say

• ?Not checked — no full text of the sourcecites Nikawa et al., 2004 source

In the paper

“may be due to the liver’s response to muscle wasting (sarcopenia).”

In the paper

“Sarcopenia is an independent risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD) cohorts, independent of obesity, inflammation, and insulin resistance (Koo et al., 2017).”

What the sources say

• ?Not checked — no full text of the sourcecites Koo et al., 2017 source

In the paper

“Oxidative stress is critical to mitochondria-mediated disease processes (Wallace, 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Wallace, 2013 source

In the paper

“and increases in renin impact circadian rhythm activity (Ohashi et al., 2017).”

What the sources say

• ?Not checked — no full text of the sourcecites Ohashi et al., 2017 source

In the paper

“Cell cycle dysfunction is heavily involved with all the other pathways discussed below.”

In the paper

“increased urinary 8-OHdG and prostaglandin F2 alpha. 8-OHdG is a biomarker of cellular oxidative stress related to DNA repair (Wu et al., 2004).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wu et al., 2004

In the paper

“Specifically, mouse ISS data (Fig. 3B), astronaut studies (Fig. 3F), and the NASA Twin Study data (Fig. 3E) all strongly support an alteration in the electron transport chain reaction and ATP production in the mitochondria.”

In the paper

“Another study reported decreased mitochondrial activity in the roots of space-flown soybean seedlings (Klimchuk, 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Klimchuk, 2007 source

In the paper

“and the lower diffusion rates of solutes in microgravity (Smith et al., 2009) reduce the hydrogen gradient at the mitochondrial intermembrane space, reducing electron transport chain and ATP synthesis (Nelson, 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Smith et al., 2009 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Nelson, 2013

In the paper

“We suggest that muscle loss may relate to the increased metabolic flux changes in spaceflight for the mouse liver versus muscle”

In the paper

“Adequate energy, protein, and vitamin D supply are essential for bone mineral density maintenance after six months of spaceflight (Smith et al., 2012b).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Smith et al., 2012b

In the paper

“inflammation leads to changes in lipid metabolism, and the persistence of the inflammatory stimulus can lead to chronic lipid changes associated with metabolic syndrome (Esteve et al., 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Esteve et al., 2005 source

In the paper

“Vitamin D3 (cholecalciferol) supplementation prevents 1,25 vitamin D loss, leading NASA to increase the vitamin D supplementation to 1000 IU/d (Douglas, 2020).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Douglas, 2020

In the paper

“cardiovascular risk is related to lipid disorders (Stein et al., 2019) and associations between dysregulation of mitochondrial energy metabolism and poor cardiac health are common (Meyers et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Stein et al., 2019 source
• ?Not checked — no full text of the sourcecites Meyers et al., 2013

In the paper

“the liver being the body’s central metabolic organ and where LDL is produced (Nelson, 2013).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Nelson, 2013

In the paper

“Lipid metabolism changes can also be caused by inflammation (Esteve et al., 2005)”

What the sources say

• ?Not checked — no full text of the sourcecites Esteve et al., 2005 source

In the paper

“since no lipid pathway changes were observed in cell line data, we suggest lipid metabolism changes are derived from complex interactions at the tissue and organ levels.”

In the paper

“The lipid/glycolytic metabolic flux imbalance occurring in liver for mice flown to space-related to the onset of fibrosis is directly involved with the mitochondrial process, which involves modulation of oxidative phosphorylation (Diamond et al., 2007) (Fig. 3B).”

What the sources say

• ?Not checked — no full text of the sourcecites Diamond et al., 2007 source

In the paper

“This would activate the ATF4 transcription factor to upregulate expression of FGF21 and GDF15 and induce the mitochondrial supercomplex assembly factor SCAF1 (Balsa et al., 2019a; Khan et al., 2017a).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Balsa et al., 2019a
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Khan et al., 2017a

In the paper

“Exercise also counteracts the effect of microgravity on the cardiovascular system; nonetheless, neither exercise intensity nor duration showed sufficient to prevent vascular changes as increased arterial and intima-media thickness, cardiac atrophy, and the development of insulin resistance (Hughson et al., 2018).”

What the sources say

• ?Not checked — no full text of the sourcecites Hughson et al., 2018 source

In the paper

“all subjects provided written informed consent”

In the paper

“All protocols were reviewed and approved by the NASA Institutional Review Board”

In the paper

“The R+0 samples were not necessarily fasting, given the time of day and nature of return from flight.”

In the paper

“In this study, the mice in space and ground control were maintained in a 12/12 light/dark cycle. They were not subjected to any workload activities that commonly impact astronauts, which rules out both possible causes for this alteration.”

In the paper

“This concept can guide new nutritional and pharmaceutical interventions and studies that will increase the viability of long-term human-crewed space missions.”

In the paper

“All available data are reported here, although the reported n for any given test or session varies for a number of reasons”

In the paper

“All samples were randomized.”

In the paper

“Resulting VdW p-values were not adjusted for multiple testing correction because of the likelihood of over-penalization of strongly dependent fluxes in and between pathways.”

In the paper

“The principal countermeasure applied to astronauts is exercise; astronauts onboard the ISS exercise for up to 2 hours per day, but there is still a considerable decrease in muscle mass, and bone loss observed after landing (Clément, 2011).”

What the sources say

• ?Not checked — no full text of the sourcecites Clément, 2011 source

In the paper

“Alteration in mitochondrial protein production would activate the mitochondrial unfolded protein response (Fig. 7A), which would trigger the integrated stress response pathway (Fig. 3C), causing phosphorylation of the cytosolic initiation factor eIF2α.”

In the paper

“G proteins are heavily involved with the renin-angiotensin system, with the activation of G proteins resulting in similar increases to the renin levels we observed (Fig. 7E). (Balakumar and Jagadeesh, 2014).”

What the sources say

• ?Not checked — no full text of the sourcecites Balakumar and Jagadeesh, 2014 source

In the paper

“Based on post-flight analysis of the RR-2 Habitat telemetry data, the ISSESs were programmed to be two degrees Celsius higher than the ISS cabin data; the result of this off-set was that the internal temperatures of the ground control habitats matched the flight Habitats closely for most of the experiment.”

In the paper

“Multiple comparisons were accounted for, and only those tests with p<0.001 are reported.”

In the paper

“At the same time, these factors increase in the liver (Fig. 6C), indicating exercise may not be enough to counteract the stressors in space.”

In the paper

“CoQ10 is currently being tested on the ISS as a countermeasure for retinal lesions, and data from this project could help elucidate if CoQ10 could be used as a more general intervention (Lulli et al., 2019).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lulli et al., 2019

In the paper

“All animal procedures performed in these experiments were approved by the Institutional Animal Care and Use Committees (IACUC) for flight at the NASA Ames Research Center (ARC) and the Kennedy Space Center (KSC) and the methods were carried out in accordance with relevant guidelines and regulations.”

In the paper

“Reduced mitochondrial function with sustained calories would generate excess mitochondrial ROS and activate compensatory mtDNA replication, resulting in increased mtDNA transcripts.”